PROJECT SUMMARY Substance use disorders (SUDs) often begin during adolescence. Mounting evidence indicates that delayed sleep phase (DSP) may confer risk for adolescent substance use (SU) and SUDs. However, the exact nature of this link and the mechanisms underlying it remain unclear. Circadian misalignment, a mismatch between late sleep hours and early school start times, is a compelling potential contributor to elevated SU in adolescent DSP with plausible neurobehavioral mechanisms. We hypothesize that DSP-associated circadian misalignment decreases impulse control and increases reward sensitivity, thereby increasing SUD risk. The proposed study will, for the first time, (1) comprehensively characterize the SUD risk profile associated with adolescent DSP, and (2) probe whether SUD risk is diminished by altering sleep/circadian timing. The study will assess both established markers of SUD risk and putative neurobehavioral mechanisms (impulsivity and reward sensitivity). Specifically, we propose a comprehensive, multi-method approach to examining DSP?s role in SUD risk, combining laboratory, experimental, and longitudinal studies. We will recruit a sample of 150 twelfth graders (17-19 y/o), divided between 100 DSP and 50 normal phase teens. We will focus on cannabis and alcohol use given their prevalent use in adolescents and evident links to DSP. The lab study compares a group of DSP adolescents to a group of normal phase adolescents on behavioral and neuroimaging (fMRI) tasks tapping impulsivity and reward sensitivity, as well as a circadian phase assessment. In the experimental study, we will probe whether stabilizing circadian phase in the DSP group by using sleep scheduling and chronotherapeutic approaches (e.g., bright light) improves sleep and neurobehavioral function relevant to SUD risk. Finally, we include repeated monthly follow-up assessments of sleep and SU to explore longitudinal associations during the high-risk transition to young adulthood. Aim 1 (Laboratory Study) is to compare a DSP group to a normal phase group on sleep/circadian factors, neurobehavioral markers, and SU. Aim 2 (Experimental Study) is to probe the impact of a sleep phase-stabilizing manipulation on sleep and circadian rhythms, as well as neurobehavioral markers of SUD risk. An Exploratory Longitudinal Aim is to!examine the prospective relationships between DSP characteristics and changes in SU via repeated monthly assessments during the high-risk transition to young adulthood. The proposed study is significant: it focuses a biologically- plausible and modifiable sleep phenotype of particular promise, during a developmental period when the mismatch between DSP and school-imposed early start times is at its worst and overall SUD risk is spiking. The proposed study is innovative: (1) it examines several promising neurobehavioral pathways to adolescent SUD, (2) it combines comprehensive and objective measures of relevant constructs, and (3) it includes an experimental manipulation to probe the mechanisms linking DSP to SUD. Finally, the proposed study will have substantial impact: it may open up novel sleep/circadian-based avenues for prevention and treatment of SUD. !